tbuckley/cabot-search huggingface dataset:
Abstract 1631: Anti-cancer effects of vorinostat on 3D cultured pancreatic cancer cells
Authors: Fatemeh Nouri Emamzaden, Beverly Word, George Hammons, Beverly D. Lyn-Cook
Journal: Cancer Research (2022)

Abstract Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive cancers, often having a low survival rate mainly due to late diagnosis and limited therapies because of drug resistance. Treatment results shown in cell models used in studying various drugs often fail in clinical trials. The lack of translation of the effects observed in vitro to patients continues to halt progress. Genetic mutations are known in PDAC; however, recent studies have suggested the role of epigenetics in its initiation and progression to a malignant phenotype. Histone deacetylase (HDAC) proteins are highly expressed in a variety of cancers, including pancreatic cancer. Recent studies have shown that targeting these proteins through the use of HDAC inhibitors may be an effective therapy for pancreatic cancer. Using a 3D cultured pancreatic cell model, anti-cancer effects by vorinostat, a HDAC inhibitor, were investigated. Although both pancreatic cell lines, PANC-1 and Mia, contain mutated K-ras and P53, a differential effect in response to vorinostat was observed in expression of cancer genes using a Human Pancreatic Adenocarcinoma TagMan Array 96 (Applied Biosystems). In the PANC-1 cell model, vorinostat decreased expression of STAT6, which is known to play a role in migration and invasion. It also decreased significantly expression of insulin growth factor 1 (IGF1), IL-6, EGF, VEGFA and TGFB1. CCND2 and CCND2 were also downregulated. In contrast, Mia cell model showed decreased expression of EGF and IGF1, but no change with the other genes. These data suggest that vorinostat has effects on several potential pathways in pancreatic cancer possibly through epigenetic mechanisms that affect certain genes involved in progression and invasion. Currently, this drug in combination with other drugs is being investigated for pancreatic cancer. Citation Format: Fatemeh Nouri Emamzaden, Beverly Word, George Hammons, Beverly D. Lyn-Cook. Anti-cancer effects of vorinostat on 3D cultured pancreatic cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1631.
Abstract 2288: A novel enzymatic fragmentation library preparation chemistry that greatly reduces sequencing artifacts
Authors: Zane Jaafar, Josh Haimes, Thomas Harrison, Lindsay Peterkin, Martin Ranik, Kristin Scott, Brian A. Kudlow
Journal: Cancer Research (2022)

Abstract After a decade of NGS technology and workflow innovation, personalized medicine is starting to become a reality. DNA fragmentation is still a critical bottleneck during library preparation. Sonication methods have been the gold standard for consistent fragmentation and uniform GC coverage, but are associated with a high upfront investment, expensive consumables, and are prone to oxidative DNA damage. On the other hand, enzymatic fragmentation methods hold the potential to be scalable, automation-friendly workflows that minimize DNA damage. Yet, typical enzymatic fragmentation methods have been shown to introduce systematic hairpin artifacts, exhibit suboptimal uniformity, and have a narrow range of input mass compatibility. We have developed a novel enzymatic fragmentation-based library preparation technology which, together with our high-fidelity library amplification module, effectively overcomes many of the key limitations of related chemistries. Libraries generated using our workflow reduced chimeric reads and terminal hairpin artifacts 10-fold compared to other enzymatic methods, and reached comparable levels of mechanically sheared DNA controls. Furthermore, we observed consistently even coverage uniformity and low sequence-specific bias for human whole genome sequencing. Fragmentation was tested across a broad sample input range from 100 pg to 500 ng. Library insert sizes were highly tunable from 150 bp to 550 bp and consistent across the input titration. High quality libraries with minimal adapter dimer were prepared from as little as 1 picogram of gDNA by adjusting the post amplification clean up conditions. Taken together, this enzymatic fragmentation and library preparation workflow avoids library preparation artifacts that convolute variant calling, is highly scalable, and suitable for ultra-low input samples. Citation Format: Zane Jaafar, Josh Haimes, Thomas Harrison, Lindsay Peterkin, Martin Ranik, Kristin Scott, Brian A. Kudlow. A novel enzymatic fragmentation library preparation chemistry that greatly reduces sequencing artifacts [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2288.
Abstract 3117: Next-generation characterization of patient-derived xenografts
Authors: Jonathan Nakashima, Long Do, Warren Andrews, Yuan-Hung Chien, Jantzen Sperry, Bianca Carapia, Deborah Yan, Giovanni Rivera, Noah Federman, Arun Singh, Fritz C. Eilber, Brian Datnow
Journal: Cancer Research (2022)

Abstract Patient-derived xenografts (PDXs) have provided the research community with dynamic and robust translational model systems to study cancer biology and accelerate drug development. To advance translational oncology, we have developed a library of PDXs and provide next-generation sequencing characterization of these models. Here, we provide mutation and transcriptomic profiles of our PDX collection along with comparisons against matched normal and cancer patient profiles. Lastly, we provide a web portal providing comprehensive genomic profiles for every PDX model to identify mutation, copy number, fusions, microsatellite status, gene expression, and enriched pathways to facilitate identification of clinically relevant models. Citation Format: Jonathan Nakashima, Long Do, Warren Andrews, Yuan-Hung Chien, Jantzen Sperry, Bianca Carapia, Deborah Yan, Giovanni Rivera, Noah Federman, Arun Singh, Fritz C. Eilber, Brian Datnow. Next-generation characterization of patient-derived xenografts [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3117.
Abstract 377: Evaluating delivery of TFR1-targeting therapies to the CNS in a novel humanized TFR1 mouse model
Authors: Chang Liu, Chengzhang Shang, Limei Ma, Xiaofei Zhou, Chaoshe Guo
Journal: Cancer Research (2022)

Abstract Transferrin receptor protein 1 (TFR1), also known as CD71, is a cell surface receptor that plays a major role in cellular iron uptake via receptor-mediated endocytosis. In mammalian species, this receptor is required for erythropoiesis and neural development. The efficient cellular uptake properties of TFR1 have been exploited for site-specific delivery of anti-cancer drugs and biologics, as well as targeted delivery of therapeutic genes to malignant cells overexpressing TFR1. Such delivery is achieved by several methods, including chemical conjugation of transferrin with therapeutic agents, genetic fusion of transferrin with peptides, and anti-TFR1 antibodies. Delivery of therapeutics cross the blood-brain barrier to the central nervous system (CNS) is also greatly facilitated by targeting the TFR1. At Biocytogen, we have successfully generated a humanized B-hTFR1 mouse model for evaluating TFR1-targeted therapeutics in preclinical studies. In this model, the exons 4-19 of mouse Tfr1 gene that encode the extracellular domain of the receptor were replaced by its human counterparts. As the result of this engineering, the ectodomain of the TFR1 is humanized while intracellular domain remains unchanged, maintaining the receptor’s signaling function in mice. Surface staining of erythroid cells from B-hTFR1 mice showed high levels of expression of humanized TFR1. In addition, we were able to detect anti-human TFR1 bispecific antibodies in brain tissues of the B-hTFR1 mouse after intravenous administration of the antibodies, suggesting a robust uptake of the antibodies via the hTFR1 receptor. These results indicate that the B-hTFR1 mouse model is a powerful preclinical tool to evaluate the delivery of therapeutics to the CNS in vivo. Citation Format: Chang Liu, Chengzhang Shang, Limei Ma, Xiaofei Zhou, Chaoshe Guo. Evaluating delivery of TFR1-targeting therapies to the CNS in a novel humanized TFR1 mouse model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 377.
Abstract 1906: Single cell precision oncology: A proof of principle
Authors: Sanju Sinha, Rahulsimham Vegesna, Alejandro Schaffer, Eytan Ruppin
Journal: Cancer Research (2022)

Abstract A combination treatment designed to target the multiple clones of a patient’s tumor could decrease the likelihood of resistant emergence. The ability to learn and predict the response of a drug at a single-cell resolution could help to design such optimal combinations. A lack of large-scale patients’ datasets with single-cell (sc) expression hinders our ability to build such models. To overcome this limitation, we built a precision oncology framework for personalized single-cell expression-based planning for treatments in oncology (PERCEPTION) that utilizes large-scale drug screens in cancer cell lines and matched bulk and single-cell transcriptome profiles to build response models that can be translated to patients. We first showed that our predicted viability profile of multiple drugs with known mechanisms of action strongly correlates with the targeted pathway activity at a single-cell resolution, demonstrating our ability to predict at this resolution. We next predict response to monotherapy and combination treatment in three independent screens performed across cancer cell lines and patient-tumor-derived cell lines using their sc-expression profiles. Translating to the clinical context, we successfully stratify responders of combination therapy in a multiple myeloma clinical trial using the tumor’s sc-expression profile. For individuals in this trial, we next find the optimal combination treatments (pairs and triplets) from the existing FDA-approved drugs set, where the pair of gefitinib and niraparib, an EGFR and a PARP inhibitor, is one of the top candidates. In sum, we provide a first-of-its-kind framework to utilize the tumor’s sc-expression to identify responders to combination therapy or to design an optimal combination for an individual patient. Citation Format: Sanju Sinha, Rahulsimham Vegesna, Alejandro Schaffer, Eytan Ruppin. Single cell precision oncology: A proof of principle [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1906.
Abstract 27: Sex biases in cancer and autoimmune disease incidence are strongly positively correlated with mitochondrial gene expression across human tissues
Authors: David Robert Crawford, Sanju Sinha, Nishanth U. Nair, Bríd M. Ryan, Jill Barnholtz-Sloan, Stephen M. Mount, Ayelet Erez, Kenneth Adalpe, Philip E. Castle, Padma S. Rajagopal, Chi-Ping Day, Alejandro A. Schäffer, Eytan Ruppin
Journal: Cancer Research (2022)

Abstract Cancer occurs more frequently in men while autoimmune diseases (AIDs) occur more frequently in women. To explore whether these sex biases have a common basis, we collected 170 AID incidence studies from many countries for tissues that have both a cancer type and an AID that arise from that tissue. Analyzing a total of 182 country-specific, tissue-matched cancer-AID incidence rate sex bias data pairs, we find that the sex biases observed in the incidence of AIDs and cancers that occur in the same tissue are positively correlated across human tissues. Second, we find that the sex bias in the expression of the 37 genes encoded in the mitochondrial genome stands out as the common key factor whose levels across human tissues are most strongly and positively associated with these incidence rate sex biases. Citation Format: David Robert Crawford, Sanju Sinha, Nishanth U. Nair, Bríd M. Ryan, Jill Barnholtz-Sloan, Stephen M. Mount, Ayelet Erez, Kenneth Adalpe, Philip E. Castle, Padma S. Rajagopal, Chi-Ping Day, Alejandro A. Schäffer, Eytan Ruppin. Sex biases in cancer and autoimmune disease incidence are strongly positively correlated with mitochondrial gene expression across human tissues [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 27.
Abstract CT512: A technology-based intervention using computers and mobile devices: To improve symptom experience of Asian American breast cancer survivors
Authors: Eun-Ok Im, Gayeong Kim, Ruiqi Jin, Mi-Yong Choi, Sudeshna Paul, Wonshik Chee
Journal: Cancer Research (2022)

Abstract Purpose: Especially with the COVID19 pandemic, the necessity of technology-based interventions using computers and mobile devices has increased in cancer survivorship management including symptom management. However, little is known about the effectiveness of a technology-based intervention in improving symptom experience of racial/ethnic minorities including Asian American breast cancer survivors. The purpose of this study was to examine the efficacy of a technology-based intervention in improving symptom experience of Asian American breast cancer survivors. Methods: This study was conducted as a part of an ongoing randomized clinical trial among 199 Asian American breast cancer survivors. The technology-based intervention included three sub-ethnic specific social media sites, interactive online educational sessions, and online resources. Both groups (intervention and control groups) used the American Cancer Society’s website on breast cancer, and only the intervention group used the technology-based intervention. Only the data collected using the questionnaire on background characteristics and health/disease status and the Memorial Symptom Assessment Scale-Short Form (MSAS) were analyzed for this study. The data were analyzed using separate intent-to-treat growth curve models. Results: While both groups reported decreases in symptom scores from the pre-test to post 3-months (p&amp;lt;.01), the intervention group had larger decreases in symptom scores compared with the control group (p&amp;lt;.01). There existed significant group * time interactive effects on the Global Distress Index (β = - 0.234), the Physical Symptom Distress scores (β = -0.266), the psychological symptom distress scores (β = - 0.212c), the total number of symptoms (β = -0.261), and the total symptom distress scores ( β = -0.261). Conclusions: The findings of this study clearly indicated symptom improvement among Asian American breast cancer survivors by a technology-based intervention using computers and mobile devices. Further studies with diverse racial/ethnic minorities are warranted to confirm the effectiveness of technology-based interventions in improving symptom experience of cancer survivors across different types of cancer. Citation Format: Eun-Ok Im, Gayeong Kim, Ruiqi Jin, Mi-Yong Choi, Sudeshna Paul, Wonshik Chee. A technology-based intervention using computers and mobile devices: To improve symptom experience of Asian American breast cancer survivors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT512.
Mapping the single-cell transcriptomic response of murine diabetic kidney disease to therapies
Authors: Haojia Wu, Romer Gonzalez Villalobos, Xiang Yao, Dermot Reilly, Tao Chen, Matthew Rankin, Eugene Myshkin, Matthew D. Breyer, Benjamin D. Humphreys
Journal: Cell Metabolism (2022)

Diabetic kidney disease (DKD) occurs in ∼40% of patients with diabetes and causes kidney failure, cardiovascular disease, and premature death. We analyzed the response of a murine DKD model to five treatment regimens using single-cell RNA sequencing (scRNA-seq). Our atlas of ∼1 million cells revealed a heterogeneous response of all kidney cell types both to DKD and its treatment. Both monotherapy and combination therapies targeted differing cell types and induced distinct and non-overlapping transcriptional changes. The early effects of sodium-glucose cotransporter-2 inhibitors (SGLT2i) on the S1 segment of the proximal tubule suggest that this drug class induces fasting mimicry and hypoxia responses. Diabetes downregulated the spliceosome regulator serine/arginine-rich splicing factor 7 (Srsf7) in proximal tubule that was specifically rescued by SGLT2i. In vitro proximal tubule knockdown of Srsf7 induced a pro-inflammatory phenotype, implicating alternative splicing as a driver of DKD and suggesting SGLT2i regulation of proximal tubule alternative splicing as a potential mechanism of action for this drug class.
Abstract 1541: LncRNA MALAT1 as a potential therapeutic target in triple negative breast cancer
Authors: Oluwatoyosi Adewunmi, Jeffrey Rosen
Journal: Cancer Research (2022)

Abstract In the United States 1 in 8 women will be diagnosed with breast cancer within their lifetime, accounting for nearly 30% of cancer diagnoses annually. Although improvements have been made in early diagnoses and treatment, the heterogeneity of breast cancer often makes treatment of the disease a challenge. Triple negative breast cancer (TNBC) ranks as the 5th leading cause of cancer related death in women, while also being more prevalent in younger African American and Hispanic premenopausal women. The invasive nature of TNBC increases the risk of metastasis and recurrence, and patients will often acquire resistance to existing treatment options, emphasizing the need for new breast cancer therapies. A novel therapeutic approach is the inhibition of the highly abundant long noncoding RNA (lncRNA), metastasis-associated lung adenocarcinoma transcript (MALAT1) using an antisense oligonucleotide (ASO). MALAT1 has been shown to be upregulated in several breast cancer subtypes, increasing the migratory and invasive properties of tumor cells. Using a MALAT1 ASO in our preclinical syngeneic p53 null TNBC tumor mouse models, we were able to significantly knockdown MALAT1 RNA expression and observed a delay in primary tumor growth as well as an improvement in tumor response when used in combination with the chemotherapy drugs carboplatin or docetaxel. Additionally, immunophenotyping of tumor infiltrating lymphocytes show that MALAT1 inhibition alters the tumor microenvironment with a significant decrease in immunosuppressive CD206+ Arginase+ macrophages and myeloid derived suppressor cells (MDSC) as well as an increase in cytotoxic CD8+ T cells. The immuno-stimulatory effects of MALAT1 inhibition highlight the benefit of a MALAT1 ASO therapeutic and its potential to be used in combination with current chemotherapies and/or developing immunotherapies. Citation Format: Oluwatoyosi Adewunmi, Jeffrey Rosen. LncRNA MALAT1 as a potential therapeutic target in triple negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1541.
COVID-19 Cases and Hospitalizations Among Medicare Beneficiaries With and Without Disabilities — United States, January 1, 2020–November 20, 2021
Authors: Yan Yuan, JoAnn M. Thierry, Lara Bull-Otterson, Marshalyn Yeargin-Allsopp, Kristie E.N. Clark, Catherine Rice, Matthew Ritchey, A. Blythe Ryerson
Journal: MMWR Morbidity and Mortality Weekly Report (2022)

Approximately 27% of adults in the United States live with a disability,* some of whom qualify for Medicare benefits. Persons with disabilities are at increased risk for severe COVID-19-associated outcomes compared with the general population (1); however, existing studies have limited generalizability† or only pertain to a specific disability (e.g., intellectual) (2). Older age is also associated with COVID-19-associated hospitalization and death, but the extent to which age might contribute to increased risk for severe COVID-19-associated outcomes among persons with disabilities is unknown (3). To describe the impact of COVID-19 on persons with disabilities and whether and how age contributes to disease rates, CDC assessed COVID-19 cases and hospitalizations during January 2020-November 2021, among Centers for Medicare & Medicaid Services (CMS) Medicare beneficiaries aged ≥18 years who were either eligible because of a disability (disability-eligible§) or only eligible because of age ≥65 years (age-eligible). COVID-19 incidence and hospitalization rates were higher in the disability-eligible group (10,978 and 3,148 per 100,000 population, respectively) throughout the study period compared with the age-eligible group (8,102 and 2,129 per 100,000 population, respectively). Both COVID-19 incidence and hospitalization rates increased with age in both disability- and age-eligible beneficiaries. American Indian or Alaska Native (AI/AN) persons had the highest disability-eligible (4,962 per 100,000) and age-eligible (5,024 per 100,000) hospitalization rates. Among all other racial and ethnic groups, hospitalization rates were higher among disability-eligible than among age-eligible patients. COVID-19 incidence and hospitalization rates among disability-eligible Medicare beneficiaries were disproportionally higher than rates among age-eligible beneficiaries. Collection of disability status as a core demographic variable in public health surveillance data and identification, as well as the addition of disability questions in other existing data sources can guide research and development of interventions for persons with disabilities. Efforts to increase access to and use of COVID-19 prevention and treatment strategies, including activities that support equitable vaccine access regardless of the substantial challenges that older adults and persons with disability face, are critical to reducing severe COVID-19-associated outcomes among these groups.